The present invention, in some embodiments thereof, relates to compositions and methods for treating hematological malignancies.
Hematological malignancies affect blood, bone marrow, and lymph nodes. These malignancies typically derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B. T. NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin. Taken together, haematological malignancies account for 9.5% of new cancer diagnoses in the United States and 30,000 patients in the UK are diagnosed each year. Within this category, lymphomas are more common than leukemias.
Multiple myeloma (MM) is a B-cell malignancy characterized by accumulation of plasma cells in the bone marrow, associated with end-organ damage that can include lytic bone lesions, anemia, immunodeficiency, and decreased renal function. MM accounts for 10% of all hematologic malignancies. It represents 1% of all cancer diagnoses, the most common malignant bone tumor and 2% of all cancer deaths [1-4].
Treatments utilizing cytotoxic chemotherapy, including alkylating agents, corticosteroids or high-dose chemotherapy followed by autologous stem cell transplantation, proteasome inhibitors and thalidomide analogues, have resulted in significant survival benefits, however, despite these advances, current therapies cannot eradicate the disease and relapses are frequently seen [5.6]. Although changes in the therapeutic landscape during the last 10-15 years have prolonged the median survival from 3 years to 6 years, the disease remains largely incurable [5,6].
For example, dexamethasone is a commonly used regimen for first-line treatment of MM. More recently, combinations of vincristine, doxorubicin, and dexamethasone (VAD) have been used to treat multiple myeloma. However, these are not effective long-term treatments. Dexamethasone treatment has a response rate of approximately 25-35%. In many patients, high-dose chemotherapy supported by autologous stem cell transplantation (ASCT) may prolong event-free survival if the procedure is performed within 12 months of initial diagnosis. However almost all patients receiving high-dose chemotherapy and an autologous peripheral stem cell transplant will ultimately relapse.
Hence, the pursuit for novel therapeutics against hematological malignancies in general and MM in particular is critically important.